The specific aims of this proposal are to quantitate the interactions of immune complexes with cultured synovial tissue cells from patients with rheumatoid arthritis (RA) and non-rheumatoid joint diseases or traumatic injury. Immune complexes are abundant in synovial fluid of patients with RA and have also been demonstrated within synovial cells. It seems likely that interactions between synovial cells and immune complexes may be important to the pathological functions of cells in RA. Synovial cell proliferation and formation of pannus are essential parts of the disease process in RA. Initiation and perpetuation of synovial cell pathological functions and the chronic inflammatory response may be partially related to the interactions of these cells with immune complexes. In the work proposed here, primary cultures of synovial tissue cells from patients with RA (RSC) will be compared to those from patients with non-rheumatoid disease or traumatic injury (NSC). Uptake and digestion of a variety of insoluble immune complexes by these cultures will be quantitated. The substrates will include: horseradish perioxidase-anti-horseradish peroxidase, heat aggregated 3H-IgG, heat aggregated 3H-IgG-rheumatoid factor and 125I-bovine serum albumin-anti-bovine serum albumin. The mechanism(s) of uptake of these complexes will be investigated using metabolic inhibitors, competitive inhibition with heat aggregated IgG, purified C3, and formation of complexes with F(ab')2 fragments. Following uptake, secretion of lysosomal enzymes, collagenase, prostaglandins and chemotactic factor and synthesis of cyclic nucleotides, will be studied. These events will also be examined in cells grown on Millipore filter-immune complex coated non-phagocytosable surfaces. In addition, the influence of anti-inflammatory agents on immune complex uptake digestion and cellular secretory and synthetic responses will be investigated. Quantitation of the interaction of synovial tissue cells with immune complexes will give us a clearer understanding of the disease process and specifically the pathological function of synovial cells in RA.